The development of neuroprotective strategies for PD is a vital unmet need. Despite remarkable advances in the last fifteen years in the understanding of pathobiological mechanisms in PD, there are no known therapies available that slow the progression or alter the course of PD. The systemic nature of PD suggests new pre-clinical approaches are needed in order to identify pathways and associated therapeutics that might slow the progression of disease. As stated in the Conference and Recommendations Report to NINDS Council (PD2014), the community of investigators focused on PD now strives to create therapies that meaningfully slow or stop the disease mechanisms that underlie all symptoms of PD. Neuroinflammation is increasingly recognized as a critically important element of PD pathogenesis. The vision for this P20 Exploratory Grant is to create the team, environment, and capability to explore innate and adaptive immunity in PD. Currently, there are no Udall Centers of Excellence that focus on understanding neuroinflammatory mechanisms in PD. These studies will require a team with a combination of specialized expertise in neuroimmunology and neurodegenerative disorders. We request support to foster the development of new collaborations and to develop critical data both in PD subjects as well as in recently developed pre-clinical models of PD. The investigative team includes two established investigators in PD (Drs. David Standaert and Andrew West), and an established investigator from the field of neuroimmunology (Dr. Etty Tika Benveniste). We will explore neuro-inflammatory signaling, particularly the actions of myeloid cells, in pre-clinical models of PD as well as early human disease. It is expected that success in these exploratory studies will lead to the development of a future Udall Center of Excellence dedicated to understanding the roles of the innate and adaptive immune system in PD, with emphasis on pursuing points of therapeutic mediation and novel neuroprotection strategies.